This application is in response to the RFA DK02-023 "Innovative Partnerships in Type 1 Diabetes Research". We are requesting support to establish formal collaboration between the Diabetes Autoimmunity Study in the Young (R01 DK32493, Marian Rewers P.I., University of Colorado) and the Virus Identification and Discovery Program (Drs. Ian Lipkin and Thomas Briese, Columbia University). Drs. Lipkin and Briese are established investigators in the field infectious diseases and pathogen discovery, however, new to diabetes research. They will be responsible for developing a comprehensive pathogen identification system for Picornaviridae and Reoviridae (specific aims 1-3). Dr. Rewers brings in expertise in epidemiology and pathogenesis of type 1 diabetes. The Diabetes Autoimmunity Study in the Young (DAISY) began in July 1993 and is currently funded until 6/2006 to establish and follow up two unique cohorts of very young children who are at a greatly increased risk of type 1 diabetes (T1DM): 1) a cohort of 693 siblings and offspring of persons with T1DM and 2) a cohort of 1,069 newborns with TIDM-associated HLA-DR,DQ alleles, identified through a newborn screening of over 25,000 general population children without a diabetic relative. This study will be the source of biological specimens to be tested in the specific aim 4: Specific Aims 1. Identify nucleic acid sequences and establish reagents to use in cDNA microarray, DSDD, and MB-BFC assays for Picornaviridae and Reoviridae 2. Establish cDNA microarrays for detection of viral transcripts 3. Establish assays for detection of viral transcripts a) DSDD assays b) MB-BFC assays Apply high throughput molecular diagnostic methods to investigate Picornaviridae and Reoviridae infections in genetically susceptible children followed prospectively from birth to type I DM